Chronic hepatitis B (CH-B), which is the leading cause of end stage liver disease and hepatocellular carcinoma worldwide, affects an estimated 10% of HIV-infected persons. The current options for treating CH- B have poor efficacy. As antiretroviral therapy is introduced into areas with the greatest burden of CH-B, it is important to determine the treatment for HBV in the HIV-infected person. To this end, the overall hypothesis tested in this proposal is that an anti-HBV regimen that has greater potency and higher resistance threshold is superior to one without both those characteristics. This hypothesis will be tested in a clinical trial nested within an existing international ACTG antiretroviral therapy (ART) trial in which participants are randomized to one of three antiretroviral regimens. One regimen contains two anti-HBV drugs in one pill and thus may have greater potency and higher resistance threshold than the other two arms. The first aim investigates the immunologic control of CH-B in HIV-infected persons by determining the relationship between the degree of immunosuppression and the amount of HBV replication. The second aim tests the hypothesis that the anti-HBV regimen that is potent and has a high barrier to resistance is superior to the other two regimens that have a lower barrier to resistance using viral suppression as the primary outcome. Viral suppression is defined using the HBV DNA assay and is measured every 6 months for 30 months minimum. Secondary outcomes include decline in HBV DNA, HBeAg seroconversion, and ALT normalization. This aim also determines HBV and HIV factors associated with response to anti-HBV treatment. The third aim tests the hypothesis that virological rebound and lack of suppression are due to development of drug-resistant virus. To accomplish this aim the entire HBV genome will be sequenced at the time of relapse and followed prospectively for the development of compensatory mutations. These mutant viruses will be tested for anti-viral drug sensitivity and replication competence. This proposal is directly relevant to public health since it addresses optimal treatment of CH-B in HIV- infected persons, which is a major global problem. This proposal has a high likelihood for success given the investigative team's experience, the randomized clinical trial design, and the nesting in an existing study. [unreadable] [unreadable] [unreadable]